Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
1] Laboratory of Pediatric Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland. [2] Basel University's Hospital, Basel, Switzerland.
Nat Immunol. 2014 Jun;15(6):554-61. doi: 10.1038/ni.2869. Epub 2014 Apr 13.
Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the appropriate microenvironment for negative selection and maturation of immunocompetent T cells with a self-tolerant T cell antigen receptor repertoire. Cues that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis factor (TNF) superfamily expressed on developing thymocytes. Here we demonstrate a negative role of the morphogen TGF-β in tempering these signals under physiological conditions, limiting both growth and function of the thymic medulla. Eliminating TGF-β signaling specifically in TECs or by pharmacological means increased the size of the mTEC compartment, enhanced negative selection and functional maturation of medullary thymocytes as well as the production of regulatory T cells, thus reducing the autoreactive potential of peripheral T cells.
髓质胸腺上皮细胞（mTEC）对于建立和维持适当的微环境至关重要，可使具有自身耐受 T 细胞抗原受体库的免疫活性 T 细胞进行阴性选择和成熟。指导 mTEC 增殖和成熟的信号由发育中的胸腺细胞上表达的肿瘤坏死因子（TNF）超家族成员提供。在这里，我们证明了形态发生素 TGF-β 在生理条件下对这些信号的负调节作用，限制了胸腺髓质的生长和功能。特异性地在 TEC 中或通过药理学手段消除 TGF-β 信号会增加 mTEC 区室的大小，增强了骨髓胸腺细胞的阴性选择和功能成熟以及调节性 T 细胞的产生，从而降低了外周 T 细胞的自身反应性潜能。
